1. Field of the Invention
The present disclosure relates to the field of drug delivery, and more particularly to the use of an enhancer to enhance the permeation of a pharmacologically active agent through human or animal skin.
2. Description of Related Art
Phosphodiesterase (PDE) is an enzyme found in various tissues. The interest in PDEs as molecular targets of drug action has grown with the development of isozyme-selective PDE inhibitors that offer potent inhibition of selected isozymes without the side-effects attributed to nonselective inhibitors. Sildenafil, vardenafil and tadalafil are inhibitors of cGMP-specific phosphodiesterase type 5 (PDE-5).
PDE-5 inhibitors are used to treat primary pulmonary hypertension (PPH), which is a disease in which blood vessels in the lungs become abnormally narrow; and erectile dysfunction. There are now three oral formulation containing PDE-5 inhibitors for treating erectile dysfunction (ED), they are Viagra (containing sildenafil) by Pfizer, Levitra (containing vardenafil) by Bayer Pharmaceutical and Glaxo-Smith-Kline-Beecham/Schering Plough, and Cialis (containing tadalafil) by Lilly-ICOS.
Although oral delivery is a convenient and non-invasive way of delivering a pharmacologically active compound, yet it has its own disadvantages. For example, it is slow acting, for the drug would have to go through the gastrointestinal system of the recipient before it can reach the intended target site such as penis for ED treatment. Further, it is more likely to cause a number of side-effects, for the drug will be circulated systematically instead of exerting its function locally.
Transdermal delivery is a feasible solution to the above-identified disadvantages of oral formulation of PDE-5 inhibitors. Various substances are known to enhance the ability of drugs and agents to diffuse through the skin and other tissues. The more popular approach has been the employment of surface active agents. However, many surface active agents enhance the permeability by actually damaging the barrier tissue. Only slight to moderate enhancement of penetration is effected with the prior art surface active agents. Another approach is to use certain organic solvents, such as dimethylsulfoxide (DMSO), dimethyl formamide (DMF) or N,N-dimethylacetamide, to enhance the penetration of active substances through stratum corneum. A disadvantage of using these solvents is that they are systemically distributed in a short period of time and cause undesirable side effects.
Thus, it would be desirable to provide an improved transdermal formulation that overcomes the above-identified deficiency. Accordingly, this invention identifies several compounds that may enhance transdermal delivery of PDE-5 inhibitors, hence are useful for the development of an improved medicament for treating conditions or diseases mediated by PDE-5.